Reduced Carotenoid and Retinoid Concentrations and Altered Lycopene Isomer Ratio in Plasma of Atopic Dermatitis Patients

Abstract

Carotenoids and retinoids are known to alter the allergic response with important physiological roles in the skin and the immune system. In the human organism various carotenoids are present, some of which are retinoid precursors. The bioactive derivatives of these retinoids are the retinoic acids, which can potently activate nuclear hormone receptors such as the retinoic acid receptor and the retinoid X receptor. In this study, we aimed to assess how plasma carotenoid and retinoid concentrations along with the ratio of their isomers are altered in atopic dermatitis (AD) patients (n = 20) compared to healthy volunteers (HV, n = 20). The study indicated that plasma levels of the carotenoids lutein (HV 198 ± 14 ng/mL, AD 158 ± 12 ng/mL, p = 0.02; all values in mean ± SEM), zeaxanthin (HV 349 ± 30 ng/mL, AD 236 ± 18 ng/mL, p ≤ 0.01), as well as the retinoids retinol (HV 216 ± 20 ng/mL, AD 167 ± 17 ng/mL, p = 0.04) and all-trans-retinoic acid (HV 1.1 ± 0.1 ng/mL, AD 0.7 ± 0.1 ng/mL, p = 0.04) were significantly lower in the AD-patients, while lycopene isomers, α-carotene, and β-carotene levels were comparable to that determined in the healthy volunteers. In addition, the ratios of 13-cis- vs. all-trans-lycopene (HV 0.31 ± 0.01, AD 0.45 ± 0.07, p = 0.03) as well as 13-cis- vs. all-trans-retinoic acid (HV 1.4 ± 0.2, AD 2.6 ± 0.6, p = 0.03) were increased in the plasma of AD-patients indicating an AD-specific 13-cis-isomerisation. A positive correlation with SCORAD was calculated with 13-cis- vs. all-trans-lycopene ratio (r = 0.40, p = 0.01), while a negative correlation was observed with zeaxanthin plasma levels (r = -0.42, p = 0.01). Based on our results, we conclude that in the plasma of AD-patients various carotenoids and retinoids are present at lower concentrations, while the ratio of selected lycopene isomers also differed in the AD-patient group. An increase in plasma isomers of both lycopene and retinoic acid may cause an altered activation of nuclear hormone receptor signaling pathways and thus may be partly responsible for the AD-phenotype.

Keywords: RAR; RXR; carotene; lycopene; retinoic acid; retinoid; vitamin A.

Figure 1

In this clustered image map analysis individual correlations between two values are displayed based on the determined concentrations and calculated ratios and percentile amounts originating from n = 40 individuals (healthy volunteers and AD-patients). A specific correlation value is indicated by a two-dimensional colored image (red to blue), where each entry of the matrix is colored on the basis of its correlation value indicated by the displayed color legend in a distance matrix analysis from plasma levels of the carotenoids zeaxanthin (ZEA), lutein (LUT), β-carotene (BCAR), α-carotene (ACAR), all-trans-lycopene (ATLYC), 13-cis-lycopene (13CLYC), 9-cis-lycopene (9CLYC), 5-cis-lycopene (9CLYC) and the retinoids 13-cis-retinoic acid (13CRA), all-trans-retinoic acid (ATRA), retinol (ROL) levels in addition to calculated ratios and percentile amounts of selected carotenoids or retinoids with the clinical AD-markers, like number of eosinophils as percentage from PBMCs (%-EOS), plasma total IgE levels in kilounits per liter (IgE), and SCORAD units [45,46]. Significant correlations are indicated by a p > 0.05 and were additionally marked by a black frame.